Methods and compositions for improving gut microbiota population

ABSTRACT

A method and a composition for improving gut micro biota structure, selectively increase a first gut microbiota population while simultaneously decrease a second gut micro biota population in a subject. The first gut micro biota population includes a short-chain fatty acid (SCFA)-producing bacterium and the second gut microbiota population includes an endotoxin-producing bacterium.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a national stage application of International application number PCT/CN2013/076709, filed Jun. 4 2013, titled “Methods and Compositions for Improving Gut Microbiota Population,” which claims the benefit of the filing date of Chinese Patent Application No. 201210185004.2 filed Jun. 6, 2012, the entire disclosure of which is incorporated by reference herein.

SEQUENCE LISTING

The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is Sequence listing.txt. The text file is about 87 KB, was created on Dec. 18, 2014, and is being submitted electronically via EFS-Web.

TECHNICAL FIELD

The present application relates to compositions and methods for improving gut microbiota populations and related application in drugs, nutritional supplements, health care products, food and beverage.

BACKGROUND

Unless otherwise indicated herein, the materials described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.

Inside the human body lives a large number of symbiotic microbes, among which the gut microbiota acts asan important environmental factor to host health. There are more than 1000 species of bacteria, whose number exceeds 10 folds of the number of human cells, and whose gene number is about 150 folds of that in human cells. In this context, the human body as a “superorganism” made of host cells and symbioticmicrobes including gut microbiota, and the genome encoding a consortium of gut microbes (microbiome) is considered as the second human genome, also known as “humanmetagenome”. When human health status changes, the composition of symbioticmicrobes changes accordingly. Conversely, changes in the composition of symbioticmicrobes lead to the change in the human health status. Together, the diversity in human genome and the genome of gut microbiome affects immunity, nutrition, metabolism, and the health and disease status of the human host. However, up to now, it is not clear by what mechanisms the gut microbiota contribute to disease etiology and pathology, which type of bacteria is positively correlated with the health status of the host, and which type of bacteria is negatively correlated with the health status of the host.

SUMMARY

The following summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.

In one aspect, the application provides methods for improving gut microbiota population. In one embodiment, the method includes administering to a subject a composition to increase a first gut microbiota population while simultaneously decrease a second gut microbiota population in the subject. The first gut microbiota population may include a short-chain fatty acid (SCFA)-producing bacteria. The second gut microbiota population may include an endotoxin-producing bacterium.

In another aspect, the application provides methods for screening a test compound that may be active in improving gut microbiota population. In one embodiment, the method includes administering to a control subject an effective amount of a control composition to increase a first gut microbiota population while simultaneously decrease a second gut microbiota population in the control subject, administering to a test subject an amount of a test compound, and comparing the gut microbiota population of the controlled subject with the gut microbiota population of the test subject. A similarity of at least about 80% is indicative that the test compound is active in improving gut microbiota population. The first gut microbiota population may include a short-chain fatty acid (SCFA)-producing bacteria. The second gut microbiota population may include an endotoxin-producing bacterium.

In a further aspect, the application provides compositions for improving gut microbiota population. In one embodiment, the composition is capable of selectively increasing a first gut microbiota population while simultaneously decreasing a second gut microbiota population in a subject. The first gut microbiota population may include a short-chain fatty acid (SCFA)-producing bacteria. The second gut microbiota population may include an endotoxin-producing bacterium. In one embodiment, the composition is administered to the subject at a dosage of from about 50 mg/kg body weight to about 400 mg/body weight and with once a day administration for at least two weeks.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments arranged in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

FIG. 1 illustrates the effect of berberine on the rat gut microbiota structure; FIG. 1A is the PCoA score plot of changes in the rat gut microbiota structure in response to HFD feeding and berberine administration; FIG. 1B shows the clustering of the gut microbiota based on mahalanobis distances calculated using MANOVA; and FIG. 1C shows the Shannon-Wiener index, calculated after rarefying to an equal number of sequence reads for all samples;

FIG. 2 illustrates some representative differences in the gut microbiota structure caused by berberine treatment using distance triplot of the RDA of gut microbiota;

FIG. 3 illustrates the effect on the short-chain fatty acid contents in rat feces when the rats were fed with high fat diet or normal chow diet; FIG. 3A shows the levels of total short-chain fatty acids (SCFAs); FIG. 3B shows the level of acetic acid; FIG. 3C shows the level of propionic acid; and FIG. 3D shows the level of butyric acid (D);

FIG. 4 illustrates the effect of berberine on obesity phenotypes and food intake in rats; FIG. 4A shows the effect of berberine on the body weight gain; FIG. 4B shows the effect of berberine on the adiposity index, calculated as the fat pad weight (sum of epididymal and perirenal fat pads) per 100 g of total body weight; and FIG. 4C shows the food intake of rats during the entire trial;

FIG. 5 illustrates the effect of berberine on the insulin sensitivity in rats; FIG. 5A shows the effect of berberine on fasting blood glucose (FBG); FIG. 5B shows the effect of berberine on fasting serum insulin (FINS); FIG. 5C shows the effect of berberine onhomeostasis assessment of insulin resistance (HOMA-IR) value, calculated according to the formula fasting insulin (μU/mL)×fasting glucose (mmol/L)/22.5; FIG. 5D shows the effect of berberine onoral glucose tolerance test (OGTT); and FIG. 5E shows the effect of berberine onintra-peritoneal insulin tolerance test (ITT); and

FIG. 6 illustrates the effect of berberine on the level of inflammation factors in rats; FIG. 6A shows the effect of berberine onserum lipopolysaccharide (LPS)-binding protein (LBP); FIG. 6B shows the effect of berberine onserum leptin; FIG. 6C shows the effect of berberine onserum MCP-1; and FIG. 6D shows the effect of berberine onserum adiponectin corrected for body fat.

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

This application is generally drawn, inter alia, to compositions, methods, processes, apparatus, systems, devices, and/or products related to improving gut microbiota population.

The application provides novel compositions and methods for improving gut microbiota population. The application identifies bacteria families that are closely related to host metabolism utilizing, for example, high throughput sequencing and multivariate statistical methods.

In one aspect, the application provides methods for improving gut microbiota population. In one embodiment, the method may include selectively enriching a first gut microbiota population. The first gut microbiota population may include, for example, an short-chain fatty acid (SCFA)-producing bacterium. In one embodiment, the method may include suppressing a second gut microbiota population. The second gut microbiota population may include, for example, an endotoxin-producing bacterium.

In one embodiment, the method may include the step of administering to a subject a composition. The composition may be an oral or parenteral formulation. The composition may selectively increase the first gut microbiota population while simultaneously decrease the second gut microbiota population.

The enrichment of the first gut microbiota population and suppression of the second microbiota population may be carried out simultaneously. The method may result in the prevention or treatment of metabolic syndrome including, without limitation, obesity, diabetes mellitus, insulin resistance, hyperlipoproteinemia, hyperuricemia, hepatic steatosis, hypercholesterolemia, hypertriglyceridemia, inflammation, and other disorders.

The short-chain fatty acid (SCFA)-producing bacteria inside gut are mostly beneficial bacteria. These bacteria either directly or, by increasing short-chain fatty acid inside gut, thus indirectly, perform functions including without limitation anti-inflammation, protecting intestinal barrier function, and regulating metabolism and immune system. These functions lead to the prevention or treatment of obesity, insulin resistance, diabetes, and other metabolic diseases.

Using the disclosed methods for improving gut microbiota population, the increased gut microbiota populationmay include Alistipes, Allobaculum, Bacteroides, Barnesiella, Blautia, Butyricicoccus, Butyricimonas, Dorea, Helicobacter, Hespellia, Holdemania, Lawsonia, Oscillibacter, Parabacteroides, Phascolarctobacterium, Prevotella, or Sedimentibacter. In one embodiment, the increased gut microbiota population may include Bacteroidaceae, Coriobacteriaceae, Desulfovibrionaceae, Erysipelotrichaceae, Flavobacteriaceae, Helicobacteracea, IncertaeSedis XI, IncertaeSedis XIV, Lachnospiraceae, Porphyromonadaceae, Prevotellaceae, Rikenellaceae, Ruminococcaceae, or Veillonellaceae; alternatively, the increased gut bacteria may include Campylobacterales, Desulfovibrionales, Bacteroidales, Coriobacteriales, Flavobacteriales, Clostridiales, or Erysipelotrichales; alternatively, the increased gut bacteria may include Epsilonproteobacteria, Deltaproteobacteria, Bacteroidia, Coriobacteridae, Flavobacteria, Clostridia, or Erysipelotrichi; alternatively, the increased gut bacteria may include Proteobacteria, Bacteroidetes, Actinobacteria, or Firmicutes.

For example, the increased gut microbiota population may include a bacterium whose V3 region of 16S rRNA gene sequence has at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% similarity with a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-93.

The endotoxin-producing bacteria inside gut are mostly harmful bacteria, which, either directly or indirectly by increasing endotoxin, promote inflammation, damage intestinal barrier function, and increase disorder in metabolism and immune system, as a result inducing obesity, insulin resistance, diabetes and other metabolic diseases.

According to the methods for improving gut microbiota population disclosed herein, the decreased gut bacteria may include Alistipes, Anaeroplasma, Barnesiella, Bifidobacterium, Butyricimonas, Butyrivibrio, Coprococcus, Fastidiosipila, Helicobacter, Hespellia, Marvinbryantia, Oribacterium, Oscillibacter, Prevotella, Roseburia, Ruminococcus, or TM7_genera_incertae_sedis; alternatively, the decreased gut bacteria may include Helicobacteraceae, Lachnospiraceae, Porphyromonadaceae, Prevotellaceae, Rikenellaceae, Ruminococcaceae, Anaeroplasmataceae, or Bifidobacteriaceae. In one embodiment, the decreased gut microbiota population may include Campylobacterales, Bacteroidales, Clostridiales, Anaeroplasmatales, or Bifidobacteriales; alternatively, the decreased gut bacteria may include Epsilonproteobacteria, Alphaaproteobacteria, Bacteroidia, Clostridia, Actinobacteridae, or Mollicutes. In one embodiment, the decreased gut microbiota population may include Proteobacteria, Bacteroidetes, Actinobacteria, Firmicutes, or Tenericutes.

For example, the decreased gut bacteria may include a bacteria whose V3 region of 16S rRNA gene sequence has at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% similarity with a nucleic acid sequence selected from a group consisting of SEQ ID NO: 94-268.

The methods may cause decrease of the serum level of pro-inflammatory factors. Example pro-inflammatory factors include without limitation cytokines such as lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, or leptin. Additionally and optionally, the methods may increase the serum level of cytokine such as adiponectin.

The level of gut short-chain fatty acids may be increased using the disclosed methods. The short-chain fatty acids may include without limitation acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid.

To improve the gut microbiota population, the compositions may be administered orally or parentally. In one embodiment, the composition may be a food, a drink, a supplement, or a pharmaceutical formulation. In one embodiment, the composition may be in the form of suppository, tablet, pill, granule, powder, film, microcapsule, aerosol, spirit, tincture, tonic, liquid suspension, or syrup. The composition may be administered at a dosage of from about 50 mg/kg body weight to about 400 mg/body weight.

In one example, the composition including berberine was administered to a subject. The gut microbiota population of the subject was then analyzed using 454 pyrosequencing techniques and the level of short-chain fatty acid was assayed by gas chromatography. The results demonstrated that berberine is capable of altering gut microbiota population: enriching certain bacteria including those that produce short-chain fatty acid while simultaneously suppressing or eliminating certain bacteria including those that produce endotoxin. It is further demonstrated that berberine administered orally is capable of increasing the level of shot-chain fatty acid inside the gut, and the increase is more pronounced in individuals who have metabolic syndrome. Additional experimentation and observation further demonstrated that above described effects by berberine on the gut microbiota population have beneficial results including without limitation improving insulin sensitivity, reducing inflammation, controlling weight gain, and preventing obesity induced by over-eating, chronic inflammation and insulin resistance.

In another aspect, the application provides methods for screening drugs, compounds, compositions, extracts, or formulations capable of improving gut microbiota population. The methods may be used in the development of drugs, nutritional supplements, health care products, food, and beverages that improve health and/or prevent obesity or other related metabolic syndromes by targeting gut microbiota population in a subject.

In one embodiment, the screening method may include administering to a control subject an effective amount of a control composition to increase the first gut microbiota population while simultaneously decrease the second gut microbiota population in the control subject, administering to a test subject an amount of a test composition, and comparing the gut microbiota population of the controlled subject and the gut microbiota population of the test subject.

As used herein, the term “subject” refers to an animal, such as a mammal, for example a human. In some embodiments, the subject may be a rat. In some embodiments, the subject may be a mouse. In some embodiments, the subject may be a human.

If the test compound demonstrates similar effect on gut microbiota as the control, the test compound is active in improving gut microbiota population. As used therein, “similar” refers to a similarity of at least about 75%, at least about 80%, at least about 90%, at least about 95%, at least about 98%, or at least about 99%.

The test composition may be a single compound, a mixture, a food, a food additive, a nutritional supplement, health care product, a pharmaceutical formulation, or a beverage.

In a further aspect, the application provides compositions for improving gut microbiota population. In one embodiment, the composition may be capable of selectively increasing the first gut microbiota population while simultaneously decreasing the second gut microbiota population in a subject.

The composition may include a chemical compound, a natural medicine, a natural product, or an herbal extract. In one embodiment, the chemical compound may include, without limitation, berberine, berberine derivatives, isoquinoline alkaloids, or any combinations thereof.

In one embodiment, the composition may include natural medicine, whole, fragmented or powdered herb, or herbal extract derived from plants of Berberis, Coptis, Scutellaria, Phellodendron, Momordica, Ilex, Sophora, Gentiana, Anemarrhena, Gardenia, Rheum, or Taraxacum. In one embodiment, the composition may include natural medicine, whole, fragmented or powdered herb, or herbal extract derived from plants of Berberidaceae, Ranunculaceae, Lamiaceae, Rutaceae, Cucurbitacea, Aquifoliaceae, Leguminosae, Gentianaceae, Agavaceae, Rubiaceae, Polygonaceae, Asteraceae, Menispermaceae, or Cucurbitaceae. In one embodiment, the composition may include natural medicine, whole, fragmented or powdered herb, or herbal extract derived from Berberis vulgaris, Coptischinensis, Scutellariabaicalensis, PhellodendriChinensis, Momordicacharantia, Ilex kudingcha, Sophoraflavescens, Gentianascabra, Anemarrhenaasphodeloides, Gardenia jasminoides, Rheum palmatum, or Herba Taraxaci.

The following examples are for illustration of the execution and property of representative method of the application. These examples are not intended to limit the scope of the application.

EXAMPLES

These examples use Wistar rats (8 weeks old, male) as testing subjects and berberine as a representative compound. 40 Wistar rats were acclimatized for two weeks and were subsequently randomly divided into four groups: normal diet group (NCD), normal diet plus berberine treatment (NCD+BBR), high fat diet (HFD), and high fat diet plus berberine treatment (HFD+BBR). Each group continued for another 18 weeks. During these 18 weeks, the NCD+BBR group received intragastric administration of berberine at stated levels. Feces samples from each animal were collected at various time points. 454 pyrosequencing was performed to analyze gut microbiota structure. Gas chromatography was used to assay the short-chain fatty acid level of the feces. In addition, weight, food intake, insulin sensitivity, systemic inflammation levels were monitored and measured during the 18-week period.

Berberine Altered the Gut Microbiota Population Under Both Normal Diet and High Fat Diet Conditions

The gut microbiota populations in rats from all four experimental groups were analyzed by 454 pyrosequencing and multivariate statistical analyses. PCoA analysis based on unweighted Unifrac distance demonstrated that berberine altered gut microbiota structure in both the normal diet group and high fat diet group at a statistically significant level; and berberine accounts for 12.6% of overall changes in the gut microbiota population (FIG. 1A). Diet also exerted statistically significant influence on gut microbiota population. FIG. 1A reveals a statistically significant difference (3.7%) in gut microbiota population between two different diets (NCD versus HFD) along the vertical axis. The multivariate variance analysis (MANOVA) on the four groups demonstrated that berberine or diet has a statistically significant influence on the gut microbiota (P<0.01), but the most pronounced difference derives from the presence of berberine (FIG. 1B). Shannon-Wiener parameter indicates that berberine reduces diversity of gut microbiota population at a statistically significant level (P<0.05).

Berberine Enriches the Short-Chain Fatty Acid-Producing Bacteria and Reduces Endotoxin-Producing Bacteria in Gut Microbiota Population

268 berberine-related OTU were identified by redundancy analysis (RDA) and the detailed results are shown in FIG. 2, TABLE 1, and TABLE 2. 93 OTU (SEQ_ID_NO 1-93) (TABLE 1) are enriched by berberine, while 175 OTU (SEQ_ID_NO 94-268) (TABLE 2) were suppressed or eliminated.

The taxonomy of these 268 OTU was analyzed using RDP classifier with representative sequence of the OTU. It was revealed that the berberine-suppressed bacteria included those of Alistipes, Anaeroplasma, Barnesiella, Bifidobacterium, Butyricimonas, Butyrivibrio, Coprococcus, Fastidiosipila, Helicobacter, Hespellia, Marvinbryantia, Oribacterium, Oscillibacter, Prevotella, Roseburia, Ruminococcus, TM7_genera_incertae_sedis, and others. Among them, the Helicobacter, belonging to Proteobacteria phylum, is capable of producing highly active endotoxin. In addition, it was revealed that the berberine-increased bacteria included those of Alistipes, Allobaculum, Bacteroides, Barnesiella, Blautia, Butyricicoccus, Butyricimonas, Dorea, Helicobacter, Hespellia, Holdemania, Lawsonia, Oscillibacter, Parabacteroides, Phascolarctobacterium, Prevotella, and Sedimentibacter. Among them, Blautia, Allobaculum, Prevotella, Bacteroides, and Butyricimonas are relatively abundant and are capable of producing short-chain fatty acid.

Therefore, when administered to a subject, berberine is capable of enriching the short-chain fatty acid-producing bacteria and reducing endotoxin-producing bacteria in gut microbiota population.

Berberine Increases Gut Short-Chain Fatty Acid Level in Rats Fed Normal Diet or High Fat Diet

The levels of short-chain fatty acid (including acetic acid, propionic acid, butyric acid, valeric acid, isobutyric acid, isovaleric acid, etc.) in rat feces were assayed by gas chromatography. The result demonstrated that oral administration of 100 mg/kg body weight may increase the level of gut short-chain fatty acid in rats fed with normal diet or high fat diet. The effect on the levels of acetic acid and propionic acid are especially pronounced (FIG. 3). Therefore, berberine is capable of increasing gut short-chain fatty acid level in rats fed normal diet or high fat diet.

Berberine Reduces Obesity Phenotype of Rats

The body weight of all four groups of rats were monitored during the duration of the experiments and analyzed. The results demonstrated that, after 18 weeks of high fat diet, the HFD group has significantly higher body weight than the normal diet group (P<0.01); intragastric administration of berberine at the dosage of 100 mg/kg effectively limits rat body weight growth, especially for rats fed high fat diet. The result is especially surprising that during the entire experimental process, the body weight of the HFD+BBR group is limited to a level similar to that of normal diet group, displaying no statistically significant difference (P>0.05). Berberine also influences, to a certain degree, the body weight of rats fed a normal diet (FIG. 4).

At the end of experiment, animals were euthanized. Fasting body weight, epididymal fat weight, and perirenal fat weight were measured. Adiposity index ([epididymal fat weight+perirenal fat]/fasting weight×100) is shown in FIG. 4B. After 18 weeks of high fat diet, the adiposity index of the HFD group is significantly higher than that of NCD, and berberine treatment significantly reduces adiposity index. Moreover, neither high fat diet nor berberine had significant effect on liver and pancreas, indicating surprisingly that long term use of berberine has no obvious side effect to rat's normal physiological function. Results of the calorie intake of these rats demonstrated that oral administration of berberine at 100 mg/kg body weight has a significant inhibitory effect on rat food intake, especially on rats fed a high fat diet (FIG. 4C).

Berberine Reduces Insulin sensitivity in Rats Fed a Normal Diet or High Fat Diet

The fasting blood glucose (FBG) and fasting insulin in serum (FINS) were measured for all four experimental groups of rats. Rats fed a HFD for 18 months had a significant higher level of FBG than that of NCD. Surprisingly, berberine effectively reduced FBG in NCD and HFD rats, especially in HFD rats where the FBG reduction was significant (P<0.05) (FIG. 5A). The result of berberine effect on insulin level is shown in FIG. 5B. The FINS of rat fed a HFD was significantly higher than that of NCD group; however, after 18 month of berberine intervention at the level of 100 mg/kg body weight, FINS level was significantly reduced even in rats fed a HFD (HFD+BBR), to reach a level comparable to that of normal diet. FIG. 5C shows the result of HOMA insulin resistance index to evaluate the insulin resistance status in rats, which demonstrates that after 18 weeks of HFD induction, rats formed apparent insulin resistance; yet berberine intervention at 100 mg/kg body weight prevented the formation of insulin resistance (P<0.05).

In order to further examine insulin sensitivity, oral glucose tolerance test and intraperitoneal injection of insulin tolerance test were conducted, and the results are shown in FIG. 5D, and 5E, respectively. Consistent with the FBG and FINS result, after 18 weeks of high fat diet inducement, oral glucose tolerance and intraperitoneal injection of insulin tolerance were significantly damaged, meanwhile, berberine intervention at 100 mg/kg body weight significantly prevented the loss of glucose tolerance and insulin tolerance, demonstrating the berberine may play an important role in improving glucosemetabolism.

Berberine Reduces Systemic inflammation Level in Rats Fed a High Fat Diet

In order to evaluate the systemic inflammation levels of all four experimental groups of rats, the serum levels of lipopolysaccharide (LPS)-binding protein (LBP), monocyte chemoattractant protein-1 (MCP-1), leptin, and adiponectin were measured, and results are shown in FIG. 6. The experiments demonstrates that HFD significantly increased LBP level in serum; but administering berberine at 100 mg/kg significantly abrogated the increase of serum LBP (P<0.05, FIG. 6A).

MCP-1 is a pro-inflammatory cytokine that functions in chemotaxis and activation of monocytes/macrophages. Occurrence and development of many inflammation-related diseases are closely related to MCP-1, including atherosclerosis, obesity, type 2 diabetes, arthritis, sepsis, and chronic bacterial infection. The results from the experiment demonstrated that, in the process of the gradual onset of obesity and insulin resistance in rat induced by HFD, MCP-1 level is gradually elevated; however, after intervention with berberine administering, MCP-1 level was significantly reduced, and, surprisingly, was even lower than that of NCD group (FIG. 6B).

Leptin is a hormone secreted by adipose tissue, and broadly participates in lipid, glucose, and energy metabolism. The results from the experiment demonstrated that serum leptin level in HFD group is significantly higher than that of NCD group (P<0.01); however, berberine significantly reduced the serum leptin level in rat, especially in rats fed a HFD (P<0.05, FIG. 6C).

The adiponectin levels in all four groups were analyzed. The results show that the adiponectin level normalized against body fat weight, was significantly lower in HFD group when compared to that of NCD group (P<0.001); however, berberine administration significantly increased adiponectin level in rats fed a HFD (P<0.01, FIG. 6D). Therefore, berberine improves gut microbiota population, reduces LPB, MCP-1, and lpetin level, and increases adiponectin secretion. TABLE 1 16S rRNA gene V3 region sequence of those bacteria enriched by berberine.

List OTUName 16S rRNA Gene V3 Region Sequence SEQ_ID_NO_ R_U00449939 TAGGGAATATTGCTCAATGGGGGAAACCCTGAAGCA 1 GCAACGCCGCGTGGAGGATGAAGGTTTTCGGATTGT AAACTCCTTTTCTAAGAGAAGATTATGACGGTATCTT AGGAATAAGCACCGGCTAACTCCGTGCC SEQ_ID_NO_ R_U01131573 GGGGAAACCCTGAAGCAGCAACGCCGCGTGGAGGAT 2 GAAGGTTTCGGATTGTAAACTCCTTTCTAAGAGAAGA TTATGACGGTATCTTAGGAATAAGCACCGGCTAACTC CGTGCC SEQ_ID_NO_ R_U00442991 TGGGGAATATTGCGCAATGGGCGAAAGCCTGACGCA 3 GCGACGCCGCGTGAGGGATGAAGGTCCTCGGATCGT AAACCTCTGTCAGGGGGGAAGAAGCGCCTGTGAGCA AATAGTTCATGGGTTTGACGGTACCCCCAAAGGAAG CACCGGCTAACTCCGTGCC SEQ_ID_NO_ R_U01131468 TGAGGAATATTGGTCAATGGGCGCAGGCCTGAACCA 4 GCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGT AAACTTCTTTTATATGGGAATAAAGTTTTCCACGTGT GGAATTTTGTATGTGCCATATGAATAAGGATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00000076 TGAGGAATATTGGTCAATGGACGAGAGTCTGAACCA 5 GCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGT AAACTTCTTTTATATGGGAATAAAGTGAGCCACGTGT GGCTTTTTGTATGTACCATACGAATAAGGATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00000261 TGAGGAATATTGGTCAATGGGCGCAGGCCTGAACCA 6 GCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGT AAACTTCTTTTATATGGGAATAAAGTTTTCCACGTGT GGAATTTTGTATGTACCATATGAATAAGGATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00277049 TGAGGAATATTGGTCAATGGGCGCAGGCCTGAACCA 7 GCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGT AAACTTCTTTTATATGGGAATAAAGTTTTCCTACGTG TGGAATTTTGTTATGTACCATATGAATAAGGATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U01140154 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCA 8 GCCAAGTAGCGTGCAGGACGACGGCCCTATGGGTTG TAAACTGTCTTTTATACGGGGATAAAGTATGCCACGT GTGGTTTATTGCAGGTACCGTATGAATAAGGACCGGC TAATTCCGTGCC SEQ_ID_NO_ R_U00797917 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCA 9 GCCAAGTAGCGTGCAGGACGACGGCCCTATGGGTTG TAAACTGCTTTTATACGGGGATAAAGTATGCCACGTG TGGTTTATTGCAGGTACCGTATGAATAAGGACCGGCT AATTCCGTGCC SEQ_ID_NO_ R_U01135802 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 10 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGCCGGGGAGGCAATGCCCACGCTCG CGAGCTGGGAAGGAGAGTACCCGGAGAAAAAGACAT CGGCTAACTCCGTGCC SEQ_ID_NO_ R_U01199632 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 11 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGCCGGGGAGCAATGCCCACGCTCGC GAGCTGGGAAGGAGAGTACCCGGAGAAAAAGACATC GGCTAACTCCGTGCC SEQ_ID_NO_ R_U01136954 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 12 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGCCGGGGAGCAAATGCCCAGCTCGC GAGCTGGGAAGGAGAGTACCCGGAGAAAAAGCATCG GCTAAACTCCGTGCC SEQ_ID_NO_ R_U01156163 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCA 13 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGTCAGGGAGCAAGAACAGGCACGT GTGCCTGACTGAGAGTACCTGAAGAAAAAGACATCG GCTAACTCCGTGCC SEQ_ID_NO_ R_U00436427 TGAGGAATATTGGTCAATGGCCGGAAGGCTGAACCA 14 GCCAAGTCGCGTGAGGGACTAAGGCCCTACGGGTCG TAAACCTCTTTTGCCGGGGAGCAATGGGGCCCTTGCG AGGGCCCAGGGAGAGTACCCGGAGAAAAAGCATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U01161731 TGAGGAATATTGGTCAATGGCCGGGAGGCTGAACCA 15 GCCAAGTCGCGTGAGGGATGACGGCCCTACGGGTTG TAAACCTCTTTTGTCGGGGAGCAAAGGACTTCACGAG TGGAGTTTCGAGAGTACCCGAAGAAAAAGACATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U00804243 TGAGGAATATTGGTCAATGGCCGGGAGGCTGAACCA 16 GCCAAGTCGCGTGAGGGATGACGGCCCTACGGGTTG TAAACCTCTTTTGTCGGGGAGCAAAGGACTTCACGAG TGGAGTTTCGAGAGTACCCGAAGAAAAAGCATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U00832647 TGAGGAATATTGGTCAATGGCCGGGAGGCTGAACCA 17 GCCAAGTCGCGTGAGGGATGACGGCCCTACGGGTTG TAAACCTCTTTGTCGGGGAGCAAAGGACTTCACGAGT GGAGTTTCGAGAGTACCCGAAGAAAGACATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00013412 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCA 18 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGTCAGGGAGCAAGAACAGGCACGT GTGCCTGACTGAGAGTACCTGAAGAAAAAGCATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U00807079 TGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCA 19 GCCAAGTCGCGTGAGGGATGACGGCCCTACGGGTTG TAAACCTCTTTTGTCGGGGAGCAAAGGACTTCACGTG TGAAGTTTCGAGAGTACCCGAAGAAAAAGCATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U00005346 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 20 GCCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTG TAAACCTCTTTTGCCGGGGAGCAATGCCGCTCTTGCG AGAGCGGAGGGAGAGTACCCGGAGAAAAAGCATCG GCTAACTCCGTGCC SEQ_ID_NO_ R_U00004086 TGAGGAATATTGGTCAATGGCCGGAAGGCTGAACCA 21 GCCAAGTCGCGTGAGGGAATAAGGCCCTACGGGTCG TAAACCTCTTTTGTCAGGGAGCAAAGCTGGCTACGCG TAGCCAGAAGGAGAGTACCTGAAGAAAAAGCATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U01130438 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 22 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTGCCGGGAGCAATGCCCAGCTCGCGAG CTGGGAAGGAGAGTACCCGGAGAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U01131459 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 23 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTGCCGGGGAGCAATGCCCAGCTCGCGA GCTGGGAAGGAGAGTACCCGGAGAAAAGACATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U00436448 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 24 GCCAAGTCGCGTGAGGGACTAAGGCCCTACGGGTCG TAAACCTCTTTTGCCGGGGAGCAAGCCGTCCCACGTG TGGGCCGGTGGAGAGTACCCGGAGAAAAAGCATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U00474862 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 25 GCCAAGTCGCGTGAGGGACTAAGGCCCTACGGGTCG TAAACCTCTTTTGCCGGGGAGCAAGCCGTCCCACGTG TGGGCCGGTGGAGAGTACCCGGAGAAAAAGACATCG GCTAACTCCGTGCC SEQ_ID_NO_ R_U00001388 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 26 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTGCCGGGGAGCAATGCCCAGCTCGCG AGCTGGGAAGGAGAGTACCCGGAGAAAAAGCATCGG CTAACTCCGTGCC SEQ_ID_NO_ R_U01185184 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCA 27 GCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTG TAAACCTCTTTTTGCCGGGGGAGCAATGCCCAGCTCG CGAGCTGGGAAGGAGAGTACCCGGAGAAAAAAGCAT CGGCTAACTCCGTGCC SEQ_ID_NO_ R_U00000528 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCA 28 GCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTTGT AAACTTCTTTTATATGGGAATAAAGTGAGGAACGTGT TCCTTTTTGTATGTACCATATGAATAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00000002 TGAGGAATATTGGTCAATGGACGAGAGTCTGAACCA 29 GCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGT AAACTTCTTTTATACGGGAATAAAGTGAGGCACGTGT GCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U00147566 TGAGGAATATTGGTCAATGGACGCAAGTCTGAACCA 30 GCCATGCCGCGTGCAGGAAGACGGCTCTATGAGTTGT AAACTGTCTTTTGTACTAGGGTAAACGCTCTTACGTG TAGGAGCCTGAAAGTATAGTACGAATAAGGATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U00000394 TGAGGAATATTGGTCAATGGACGCAAGTCTGAACCA 31 GCCATGCCGCGTGCAGGAAGACGGCTCTATGAGTTGT AAACTGCTTTTGTACTAGGGTAAACGCTTCTACGTGT AGGAGCCTGAAAGTATAGTACGAATAAGGATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U00047397 TGGGGAATTTTGCGCAATGGGGGGAACCCTGACGCA 32 GCAACGCCGCGTGCGGGATGACGGCCCTCGGGTTGT AAACCGCTTTCAGCAGGGAAGACCACGACGGTACCT GCAGAAGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000552 TGAGGAATATTGGGCAATGGGCGGAAGCCTGACCCA 33 GCCATGCCGCGTGCAGGAAGACAGCCCTATGGGTCG TAAACTGCTTTTTTAGAGGAAGAATAAAGTCTACGTG TAGACCGATGACGGTACTTTAAGAAAAAGCATCGGC TAACTCCGTGCC SEQ_ID-NO_ R_U00441706 GTAGGGAATATTGCACAATGGGGGAAACCCTGATGC 34 AGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATG TAAACTTCTATCAGCAGGGAAGACAATGACGGTACC TGACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00119974 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 35 GCGACGCCGCGTGAAGGAAGAAGTATTTCGGTATGT AAACTTCTATCAGCAGGGAAGAAAGTGACAGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00104206 TGGGGAATATTGCACAATGGGGGAAACCCGTACGAT 36 GCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTA TGTAAACTTCTATCAGCAGGGAAGATAATGACGGTA CCTGACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00580795 TGGGGAATATTGCACAATGGGGGAAACCCGTACGAT 37 GCAGCGACGCCGCGTGAAGGAAGAAGTATCTCGGTA TGTAAACTTACTATCAGCAGGGAAGATAATGACGGT ACCTGACTAAGAAGCCCCGGCCTAACTACGTGCC SEQ_ID_NO_ R_U01129900 AAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAG 38 TATCTCGGTATGTAAACTTCTATCAGCAGGGAAGACA ATGACGGTACCTGACTAAGAACGCCCGGCTAACTAC GTGCC SEQ_ID_NO_ R_U00016467 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 39 GCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGT AAACTTCTATCAGCAGGGAAGATAATGACGGTACCT GACTAAGAAGCCCCGGCTAATTACGTGCC SEQ_ID_NO_ R_U00000367 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 40 GCGACGCCGCGTGAAGGAAGAAGTATCTCGGTATGT AAACTTCTATCAGCAGGGAAGATAATGACGGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00459481 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 41 GCAACGCCGCGTGGGTGAAGGAGCGTTTCGGCGCGT AAAGCCCTGTCAGCGGGGAAGAAAAAAGACGGTACC CGACCAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000215 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCA 42 GCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGT AAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00071963 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 43 GCGACGCCGCGTGAAAGATGAAGTATTTCGGTATGT AAACTTCTATCAGCAGGGAAGAAAATGACGGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000939 TGGGGAATATTGCACAATGGAGGAAACTCTGATGCA 44 GCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGT AAAGCTCTATCAGCAGGGAAGACAGTGACGGTACCT GACTAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U00472681 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCA 45 GCGACGCCGCGTGAGTGACGAAGTATCTCGGTATGT AAAGCTCTGTCAGCAGGGAAGAAGAATGACGGTACC TGAAGAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U00000105 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCA 46 GCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGT AAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000279 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCA 47 GCAACGCCGCGTGAAGGAAGACGGTTTTCGGATTGT AAACTTCTATCAATAGGGAAGAAAGAAATGACGGTA CCTAAATAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00022935 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 48 GCAACGCCGCGTGAAGGAAGACGGTTTTCGGATTGT AAACTTCTATCAATAGGGAAGAAAGAAATGACGGTA CCTAAATAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000550 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 49 GCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGT AAACTCCTGTCCCAGGGGACGATAATGACGGTACCCT GGGAGGAAGCACCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00009280 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCA 50 GCAACGCCGCGTGAAGGAAGACGGTTTTCGGATTGT AAACTTCTGTTCTTAGTGAAGAAGAATGACGGTAGCT AAGGAGCAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00164237 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCA 51 GCAACGCCGCGTGAAGGAAGACGGTTTTCGGATTGT AAACTTCTGTTCTTAGTGAAGAATAATGACGGTAACT AAGGAGCAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00032911 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 52 GCGACGCCGAGTGAGGGAAGAAGGTTTTCGGATTGT AAACCTCTGTCCTTGGTGAAGATAATGACGGTAGCCA AGGAGGAAGCTACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00040533 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCA 53 GCGACGCCGCGTGAGGGAAGACGGCCTTCGGGTTGT AAACCTCTGTCGCAGGGGACGAAGGAAGTGACGGTA CCCTGTGAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01145869 GAATATTGCGCAATGGGGGCAACCCTGACGCAGCAA 54 CGCCGCGTGAAGGATGAAGGTTTTCGGATTGTAAACT TCTTTTATCAAGGACGAAGGACGTGACGGTACTTGAT GAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00211687 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 55 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTACCAGGGGACGAAGGACGTGACGGT ACCTGGAGAAAAAGCAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01206474 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 56 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTACCTAGGGACGAAGGACGTGACGGTA CCTGGAGAAAAAGACAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01219720 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 57 GCAACGCCGCGTGAAGGAAGAAGGTTTTCGGGTTGT AAACTTCTTTTACCAGGGACGAAGGACGTGACGGTA CCTGGAGAAAAAGCAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01210669 GACCCAGCAACGCCGCGTGAAGGAAGAAGGTCGTTT 58 CGGGTTAGTAAACTTCTTTTACCGAGGGACGAAGGAC GTGACGGTACCTGGAGAAAAAGCAACGGCTAACTAC GTGCC SEQ_ID_NO_ R_U00001394 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 59 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTACCAGGGACGAAGGACGTGACGGTA CCTGGAGAAAAAGCAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00460521 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 60 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTACCTAGGGACGAAGGACGTGACGGTA CCTGGAGAAAAAGACAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00831992 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 61 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTACCAGGGACGAAGGACGTGACGGTA CCTGGAGAAAAGACAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01143501 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCA 62 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTCTGGGGGACGAAGAAAGTGACGGTA CCCCACGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00815791 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCA 63 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTCTGGGGGGCGAAGAAAGTGACGGTA CCCCAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00043629 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCA 64 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTCTGGGGGACGAAGAAAGTGACGGTA CCCCAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00164098 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCA 65 GCAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGT AAACTTCTTTTCTCGGGGACGAACAAATGACGGTACC CGAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000374 TGGGGAATATTGCGCAATGGGGGCAACCCTGACGCA 66 GCAACGCCGCGTGATTGAAGAAGGTCTTCGGATTGTA AAAATCTTTTATCAAGGACGAAGAAGTGACGGTACTT GATGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00003296 TGGGGAATATTGGGCAATGGGGGGAACCCTGACCCA 67 GCAACGCCGCGTGAGGGAAGAAGGTTTTCGGATCGT AAACCTCTGTCCTTGGTGAAGAGGAGAAGACGGTAG CCAAGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00027329 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCA 68 GCAACGCCGCGTGAGGGAAGAAGGTTTTCGGATCGT AAACCTCTGTCCTTGGTGAAGAGAAGAAGACGGTAG CCAAGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00003420 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCA 69 GCAACGCCGCGTGAAGGATGAAGTATTTCGGTATGT AAACTTCTATCAGCAGGGAAGATAACGACGGTACCT GACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00436238 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCA 70 GCAACGCCGCGTGAACGAAGAAGGTCTTCGGATTGT AAAGTTCTGTCCTTAGGGAAGAAGAAAGTGACGGTA CCTAAGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U00439751 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCA 71 GCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGT AAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCT G SEQ_ID_NO_ R_U00004741 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCA 72 GCGACGCCGCGTGAAGGAAGAAGTATTTCGGTATGT AAACTTCTATCAGCAGGGAAGAAAATGACGGTACCT GACTAAGAAGCCCCGGCTAATTACGTGCC SEQ_ID_NO_ R_U01160251 TAGGGAATTTTTCGTCAATGGGCGCAAGCCTGAACGA 73 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAGGAAGGGAAGAG GAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01166410 TAGGGAATTTTTCGTCAATGGGCGCAAGCCTGAACGA 74 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAGGAAGGAAAGAG GAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01169117 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 75 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAAACTCTGTTGCGGGGGAAAAAAGGAAGGGAAG AGGAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAA GTCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01180557 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 76 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTTGCGGGGGGAAAAAGGAAGGGAAGA GGAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAG TCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00804007 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 77 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAGGAAGGGAAGAG GAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01143008 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 78 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGAAAAGGAAGGGAAGAGGA AATGCTTTTCTTTTGTATGGTACCCCGCCAGAAAGTC ACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01145549 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 79 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAGGAAGGGAAGAGG AAATGCTTTTCTTTTGTATGGTACCCCGCCAGAAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00808391 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 80 GCAATGCCGCGTGGGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAGGAAGGGAAGAGG AAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGTC ACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01144224 GGTAATTTTCGTCAATGGGCGCAAGCCTGAACGAGC 81 AATGCCGCGTGGGCGAAGAAGGTCTTCGGATACGTA AACTCTGTTGCGGGGGAAAAAGGAAGGGAAGAGGA AATGCTTTCTTTTGATGGTACCCCGCCAGAAAGTCAC GGCTAACTACGTGCC SEQ_ID_NO_ R_U01214804 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 82 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAGGAAGGGAAGAG GAAATGCTTTTCTTTTGATGGTACCCCGCCCAGAAAG TCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U01173110 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 83 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAAGGAAGGGAAGA GGAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAG TCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00305232 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 84 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAAGGAAGGGAAGAG GAAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00043735 TAGGGAATTTTTCGTCAATGGGCGCAAGCCTGAACGA 85 GCAATGCCGCGTGAACGAGGAAGGTCTTCGGATCGT AAAGTTCTGTTGAGAGGGAAAAAGGGTCACCAGAGG AAATGCTGGTGAAGTGATATTACCTTTCGAGGAAGTC ACGGCTAACTACGTGCC SEQ_ID_NO_  R_U00000409 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 86 GCAATGCCGCGTGAACGAGGAAGGTCTTCGGATCGT AAAGTTCTGTTGAGAGGGAAAAAGGGTCACCAGAGG AAATGCTGGTGAAGTGATATTACCTTTCGAGGAAGTC ACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00029718 GGTAATTTTCGTCAATGGGCGCAAGCCTGAACGAGC 87 AATGCCGCGTGAACGAGGAAGGTCTTCGGATCGTAA AGTTCTGTTGAGAGGGAAAAAGGGTCACCAGAGGAA ATGCTGGTGAAGTGATATTACCTTTCGAGGAAGTCAC GGCTAACTACGTGCC SEQ_ID_NO_ R_U00007185 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 88 GCAATGCCGCGTGAACGAGGAAGGTCTTCGGATCGT AAAGTTCTGTTGAGAGGGAAAAAAGGGTCACCAGAG GAAATGCTGGTGAAGTGATATTACCTTTCGAGGAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00011248 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 89 GCAATGCCGCGTGAACGAGGAAGGTCTTCGGATCGT AAAGTTCTGTTGAGAGGGAAAAGGGTCACCAGAGGA AATGCTGGTGAAGTGATATTACCTTTCGAGGAAGTCA CGGCTAACTACGTGCC SEQ_ID_NO_ R_U01156257 TAGGGAATTTTCGTCAAGTGGGCGCAAGCCTGAACG 90 AGCAATGCCGCGTGAACGAGGAAGGTCTTCGGATAC GTAAAGTTCTGTTGAGAGGAAAAAGGGTCACCAGAG GAAATGCTGGTGAAGTGATATTACCTTTCGAGGAAGT CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00808203 TAGGGAATTTTCGTCAATGGGCGCAAGCCTGAACGA 91 GCAATGCCGCGTGAGCGAAGAAGGTCTTCGGATCGT AAAACTCTGTTGCGGGGGAAAAGGAAGGGAAGAGG AAATGCTTTTCTTTTGATGGTACCCCGCCAGAAAGTC ACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00003073 TAGGGAATTTTCGGCAATGGGCGAAAGCCTGACCGA 92 GCAACGCCGCGTGAGTGAAGAAGGCCTTCGGGTTGT AAAGCTCTGTTGTGAAGGAAGAACGGCTCATAGAGG GAATGCTATGGGAGTGACGGTACTTTACCAGAAAGC CACGGCTAACTACGTGCC SEQ_ID_NO_ R_U00000235 TGGGGAATCTTCCGCAATGGACGAAAGTCTGACGGA 93 GCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTA AAGCTCTGTTGTTTATGACGAACGTGCAGTGTGTGAA CAATGCATTGCAATGACGGTAGTAAACGAGGAAGCC ACGGCTAACTACGTGCC

TABLE 2 16S rRNA gene V3 region sequence of those bacteria suppressed/eliminated by berberine. List OTUName 16S rRNA Gene V3 Region Sequence SEQ_ID_NO_ R_U0043619 TGAGGAATATTGGGCAATGGGGGCAACCCTGACCCAG 94 5 CCATGCCGCGTGAGTGAAGAAGGTTTTCGGATTGTAA AGCTCTTTCGGATGTGACGATGATGACGGTAGCATCT AAAGAAGCCCCGGCAAACTTCGTGCC SEQ_ID_NO_ R_U0010141 GNGGGAAACCCTGAAGCAGCAACGCCGCGTGGAGGA 95 6 TGAAGGTTTCGGATTGTAAACTCCTTTGTTAGAGAAG ATAATGACGGTATCTAACGAATAAGCACCGGCTAACT CCGTGCC SEQ_ID_NO_ R_U0000040 TAGGGAATATTGCTCAATGGGGGAAACCCTGAAGCAG 96 7 CAACGCCGCGTGGAGGATGAAGGTTTTCGGATTGTAA ACTCCTTTTGTTAGAGAAGATAATGACGGTATCTAAC GAATAAGCACCGGCTAACTCCGTGCC SEQ_ID_NO_ R_U0080096 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 97 6 CCAAGTAGCGTGCAGGAAGACGGCCCTACGGGTTGTA AACTGCTTTTATGCGGGGATAAAGTGCAATACGTGTA TTGCTTTGCAGGTACCGCATGAATAAGGACCGGCTAA TTCCGTGCC SEQ_ID_NO_ R_U0113198 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 98 2 CCAAGTAGCGTGCAGGATGACGGCCCTACGGGTTGTA AACTGCTTTTTTGCGGGAATAAAGCGGCTCACGTGTG AGCCTTTGCATGTACCGCACGAATAAGGACCGGCTAA TTCCGTGCC SEQ_ID_NO_ R_U0079783 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 99 9 CCAAGTAGCGTGCAGGATGACGGCCCTATGGGTTGTA AACTGCTTTTATACGGGGATAAAGTTGGGGACGTGTC CCCATTTGTAGGTACCGTATGAATAAGGACCGGCTAA TTCCGTGCC SEQ_ID_NO_ R_U0000398 TGAGGAATATTGGTCAATGGTCGTGAGACTGAACCAG 100 1 CCAAGTAGCGTGCGGGATGAAGGCCCTCCGGGTCGTA AACCGCTTTTAGACGGGGATAAAAGGGCATACGTGTA TGCCGTATTGCATGTACCGTCAGAAAAAGGACCGGCT AATTCCGTGCC SEQ_ID_NO_ R_U0000140 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 101 4 CCAAGTAGCGTGAAGGAAGACTGCCCTATGGGTTGTA AACTTCTTTTATAAGGGAATAAAGAGCGCCACGTGTG GTGTGTTGTATGTACCTTATGAATAAGCATCGGCTAAT TCCGTGCC SEQ_ID_NO_ R_U0000005 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 102 2 CCAAGCCGCGTGAGGGAAGAAGGCGCCAGGCGTCGT AAACCTCTTTTGCCGGGGAACAAAGGGCGCCACGTGT GGCGTTGTGAGTGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000096 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 103 4 CCAAGCCGCGTGAGGGAGGAAGGCGCCAGGCGTCGT AAACCTCTTTTGCCGGGGAACAAAGGGCGCCACGTGT GGCGTTGTGAGTGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0004069 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 104 0 CCAAGCCGCGTGAGGGAGGAAGGCGCCAGGCGTCGT AAACCTCTTTTGCCGGGGAACAAAGGGCGCCACGTGT GGCGTTGTGAGTGTACCCGGAGAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0082399 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 105 1 CCAAGCCGCGTGAGGGAGGAAGGCGCCAGGCGTCGT AAACCTCTTTTGCCGGGGAACAAAGGGCGCCACGTGT GGCGTTGTGAGTGTACCCGGAGAAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000080 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 106 4 CCAAGCCGCGTGAGGGAATAAGGCGCCAAGCGTCGTA AACCTCTTTTGTCAGGGAACAAAAGCGGGCACGCGTG CCCGTCCGAGTGTACCTGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0115591 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 107 5 CCAAGCCGCGTGAAGGAAGAAGGTGCTAAGCATTGTA AACTTCTTTTGTCAGGGAACAAAGAGCGCGACGAGTC GCGCCGTGAGTGTACCTGAAGAAAAAGACATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0045985 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 108 0 CCAAGCCGCGTGAAGGAAGAAGGTGCTAAGCATTGTA AACTTCTTTTGTCAGGGAACAAAGAGCGCGACGAGTC GCGCCGTGAGTGTACCTGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0079809 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 109 8 CCAAGCCGCGTGAAGGAAGAAGGTGCTAAGCATTGTA AACTTCTTTTGTCAGGGAACAAAGAGCGCGACGAGTC GCGCCGTGAGTGTACCTGAAGAAAAGCATCGGCTAAC TCCGTGCC SEQ_ID_NO_ R_U0000917 TGAGGAATATTGGTCAATGGTCGGAAGACTGAACCAG 110 0 CCAAGCCGCGTGAAGGAAGAAGGTGCTCGGCATCGTA AACTTCTTTTGTCAGGGAACAAAGGGCGGTACGTGTA CCGCTGTGAGTGTACCTGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0110215 TGAGGAATATTGGTCAATGGTCGGAAGACTGAACCAG 111 3 CCAAGCCGCGTGAAGGAAGAAGGTGCTCGGCATCGTA AACTTCTTTTGTCAGGGAACAAAGGGCGGTACGTGTA CCGCTGTGAGTGTACCTGAAGAAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000623 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 112 0 CCAAGCCGCGTGAAGGAAGAAGGTGCAGGGCATCGT AAACTTCTTTTGCCGGGGAACAATAAGCGGGACTAGT CCCGCGACGAGTGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0046534 TGAGGAATATTGGTCAATGGGCGTGAGCCTGAACCAG 113 4 CCAAGCCGCGTGAAGGAAGAAGGTGCAGGGCATCGT AAACTTCTTTTGCCGGGGAACAATAAGCGGGACTAGT CCCGCGACGAGTGTACCCGGAGAAAAGACATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000120 TGAGGAATATTGGTCAATGGTCGGGAGACTGAACCAG 114 2 CCAAGCCGCGTGAGGGATGGAGGTACAGAGTATCGTA AACCTCTTTTGTCAGGGAACAAAGGGCGCCACGTGTG GCGCTATGAGGGTACCTGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000138 TGAGGAATATTGGTCAATGGGAGAGATCCTGAACCAG 115 4 CCAAGCCGCGTGAGGGAAGACGGCACTACGTGTTGTA AACCTCTTTTGCCGGGGAACAAAAGCGGGGACGCGTC CCCGTCCGCGTGTACCCGGAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0080279 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 116 9 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGAGCGCCACGCGTG GCGAGATGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0080845 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 117 3 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGAGCGCCACGCGTG GCGAGATGAGAGTACCCGAAGAAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0002671 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 118 1 CCAAGCCGCGTGAAGGAAGACGGCCCTACGGGTTGTA AACTTCTTTTGTTGCAGGACAACACCCCGGACGCGTCC GGGCATGAGTGTATGCAAAGAAAAAGCATCGGCTAAC TCCGTGCC SEQ_ID_NO_ R_U0000065 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 119 0 CCAAGCCGCGTGAGGGAATAAGGCCCTACGGGTCGTA AACCTCTTTTGTCGGGGAACAAAACCGGAGACGAGTC TCCGGCTGCGTGTACCCGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000083 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 120 9 CCAAGCCGCGTGAGGGAAGAAGGCGCTCAGCGTCGTA AACCTCTTTAGCCGGGGAACAAAGAGCTGCTCGGGAA GCAGCGTTGAGCGTACCCGGAGAATAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0115793 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 121 0 CCAAGTCGCGTGAGGGACGACGGTCCTACGGATTGTA AACCTCTTTTGCCGGGGAGCAATGCGCGGTACGCGTA CCGCGACGGAGAGTACCCGGAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0079842 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 122 0 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGAGCGCCACGCGTG GCGAGATGAGAGTACCCGAAGAAAAGACATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000193 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAG 123 3 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAGGACTGCCACGAGTG GCAGGGCGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000149 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 124 1 CCAAGTCGCGTGAGGGAAGACGGTCTTACGGATTGTA AACCTCTTTTGCCGGGGAGCAAAGGGCGCCACGCGTG GCGTTTCGAGAGTACCCGGAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000647 TGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAG 125 6 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAAAGGCGTCACGTGTG ACGCTATGAGAGTACCCGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000150 TGAGGAATATTGGTCAATGGCCGGAAGGCTGAACCAG 126 2 CCAAGCCGCGTGAGGGAGGAAGGCGCAGAGCGTCGC AGACCTCTTTTGCCGGGGGACAAAAGGCCGGACTCGT CCGGTCCTGAGGGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000150 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAG 127 4 CCAAGTCGCGTGAGGGATGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAATTCCGTTACGTGTAA CGGAGTCGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000060 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 128 9 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGCAGGGGAGCAAGGCACGGTACGTGTA CCGTGAAGGAGAGTACCCTGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000926 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 129 1 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCTCACGTGTG AGCGGAAGGAGAGTACCCGAAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0113699 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 130 2 CCAAGTCGCGTGAGGGAGGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCTCACGTGTG AGCGGAAGGAGAGTACCCGAAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000049 TGAGGAATATTGGTCAATGGCCGAAGGGCTGAACCAG 131 7 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGCCGGGGAGCAAAGGCGGTCACTGGTG ACCGGATGAGAGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000088 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 132 6 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCAGGGAGCAAGGAGGGCCACGAGTG GCGCTTCGGAGAGTACCTGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0114329 TGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAG 133 2 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAACAGCGCAACGCGCT TGCGCATTGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0080318 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 134 8 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGAGCGCCACGCGTG GCGAGATGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000878 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 135 2 CCAAGTCGCGTGAGGGAAGACGGCCCTATGGGTTGTA AACCTCTTTTGCCGGGGAGCAAAGAACCGCACGTGTG CGGTCTGGAGAGTACCCGGAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000140 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 136 6 CCAAGTCGCGTGAGGGAATAAGGCCCTAAGGGTCGTA AACCTCTTTTGCCGGGGAGCAATGGTTCGCTTGCGAG CGGACAGGGAGAGTACCCGGAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0003088 TGAGGAATATTGGTCAATGGCCGTAAGGCTGAACCAG 137 0 CCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTA AACCTCTTTTGCCGGGGAGCAAAAGGCGCCACGCGTG GCGTTTCGAGAGTACCCGGAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0045093 TGAGGAATATTGGTCAATGGGCGTAAGCCTGAACCAG 138 8 CCAAGTCGCGTGAGGGAAGACGGCCCTATGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCCCACGTGTG GGCGGAAGGAGAGTACCCGAAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000976 TGAGGAATATTGGTCAATGGGCGTAAGCCTGAACCAG 139 3 CCAAGTCGCGTGAGGGAAGACGGCCCTATGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCCCACGAGTG GGCGGAAGGAGAGTACCCGAAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0115549 TGAGGAATATTGGTCAATGGGCGTAAGCCTGAACCAG 140 5 CCAAGTCGCGTGAGGGAAGACGGCCCTATGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCCCACGAGTG GGCGGAAGGAGAGTACCCGAAGAAAAAGACATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U0079869 TGAGGAATATTGGTCAATGGGCGTAAGCCTGAACCAG 141 4 CCAAGTCGCGTGAGGGAAGACGGCCCTATGGGTTGTA AACCTCTTTTGTCGGGGAGCAAAGCCGCCCACGAGTG GGCGGAAGGAGAGTACCCGAAGAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0080236 TGAGGAATATTGGTCAATGGGCGGTAGCCTGAACCAG 142 0 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGCCGGGGAGCAAGGCCATGTACGTGTA CGTGGCCTGAGAGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0116278 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAG 143 2 CCAAGTCGCGTGAGGGAAGACGGTCCTAAGGATTGTA AACCTCTTTTGTCAGGGAGCAAGGAGCGCCACGTGTG GCGCGGCGAGAGTACCTGAAGAAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000270 TGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAG 144 9 CCAAGTCGCGTGAGGGAAGACGGTCCTAAGGATTGTA AACCTCTTTTGTCAGGGAGCAAGGAGCGCCACGTGTG GCGCGGCGAGAGTACCTGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000523 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 145 2 CCAAGTCGCGTGAGGGAAGACAGTCCTATGGATTGTA AACCTCTTTTGCCGGGGAGCAAAGAGCGGCACGTGTG CCGCGCCGAGAGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000030 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 146 5 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGCCGGGGAGCAAAGAGCGGCACGTGTG CCGCGCCGAGAGTACCCGGAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0000682 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 147 1 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAACGAAGGCACGTGTGC CAGAAGCGAGATTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0119940 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 148 5 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAACGAAGGCACGTGTGC CAGAAGCGAGATTACCCGAAGAAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000615 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 149 0 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAACGAAGGCACGTGTGC CTGAAGCGAGATTACCCGAAGAAAAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000020 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 150 6 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAAGAGGCCACGTGTGG TCAAAAGCGAGAGTACCCGAAGAAAAAGCATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0115067 TGAGGAATATTGGTCAATGGGCGGGAGCCTGAACCAG 151 3 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAAGAGGCCACGTGTGG TCAAAAGCGAGAGTACCCGAAGAAAAAGACATCGGC TAACTCCGTGCC SEQ_ID_NO_ R_U0080581 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 152 1 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAGGATCCGCACGAGTG CGGAGGCGAGAGTACCCGAAGAAAAAGCATCGGCTA ACTCCGTGCC SEQ_ID_NO_ R_U0119947 TGAGGAATATTGGTCAATGGGCGGAAGCCTGAACCAG 153 1 CCAAGTCGCGTGAGGGAAGACGGTCCTATGGATTGTA AACCTCTTTTGTCGGGGAGCAAGGATCCGCACGAGTG CGGAGGCGAGAGTACCCGAAGAAAAAGACATCGGCT AACTCCGTGCC SEQ_ID_NO_ R_U0000006 TGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAG 154 8 CCAAGTCGCGTGAGGGAAGAATGGTCTATGGCCTGTA AACCTCTTTTGTCAGGGAAGAATAAGGATGACGAGTC ATTCGATGCCAGTACTTGACGAATAAGCATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0000555 TGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAG 155 9 CCATGCCGCGTGCAGGAAGACGGCTCTATGAGTTGTA AACTGCTTTTGTACGAGGGTAAACCCGGATACGTGTA TCCGGCTGAAAGTATCGTACGAATAAGGATCGGCTAA CTCCGTGCC SEQ_ID_NO_ R_U0080196 CTAAGGATATTCCGCAACGGGCGGAAGCCCGGCGGAG 156 1 CGACGCCGCGTGGACGAGGAAGGCCGGAAGGTTGCA GAGTCCTTTTGCGGGGGAAGAAGGAGCCGCGGAGGG AATGCCGCGGCGGCGACCGAACCCCGCGAATAAGGG GCGGCTAATTACGTGCC SEQ_ID_NO_ R_U0000012 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAG 157 6 CGACGCCGCGTGCGGGATGGAGGCCTTCGGGTTGTAA ACCGCTTTTGTTCAAGGGCAAGGCACGGCTTCGGGCC GTGTTGAGTGGATTGTTCGAATAAGCACCGGCTAACT ACGTGCC SEQ_ID_NO_ R_U0016410 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 158 5 CGACGCCGCGTGGGTGAAGAAGTATTTCGGTATGTAA AGCCCTATCAGCAGGGAAGAAAAAGACGGTACCTGA CTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0011807 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 159 8 CGACGCCGCGTGAAGGAAGAAGTATTTCGGTATGTAA ACTTCTATCAGCAGGGAAGAAAATGACGGTATCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0114837 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 160 6 CGACGCCGCGTGGGTGAAGAAGTATTTCGGTATGTAA AGCCCTATCAGCAGGGAAGAAAATGACAGTACCTGAA TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0044400 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 161 2 CGACGCCGCGTGGGTGAAGAAGTATTTCGGTATGTAA AGCCCTATCAGCAGGGAAGAAAGAAGACGGTACCTG AGTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0113039 TGGGGAGTATTGCACAATGGGGGAAACCCGTGATGCA 162 6 GCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTA AAGCTCTATCAGCAGGGAAGAAAATAGACGGTACCTG ACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0001158 TGGGGGATATTGGACAATGGGGGGAACCCTGATCCAG 163 2 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAGAAATGACGGTACCT GACCAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0043988 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 164 8 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTACGTAA AGCTCTATCAGCAGGGAAGAAAAAGAAATGACGGTA CCTGATTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0116361 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 165 7 CAATGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAAAAGACGGTACCTG ACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0002930 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 166 6 CAATGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAAAAGACGGTACCTG ACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0079798 TGGGGAATATTGCACAATGGAGGAAACTCTGATGCAG 167 5 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTACGTAA AGCTCTATCAGCAGGGAAGAAAAAATGACGGTACCTG ACTAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0117359 TGGGGAATATTGCACAATGGAGGAAACTCTGATGCAG 168 4 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTACGTAA AGCTCTATCAGCAGGGAGAAAAAAATGACGGTACCTG ACTAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0000928 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 169 2 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAGATGACAGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016528 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 170 8 CAACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0000348 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 171 1 CGATGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAA ACTCCTGTCTTAAAGGACGATAATGACGGTACTTTAG GAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000354 TGGGGAATATTGCACAATGGGCGCAAGCCTGATGCAG 172 8 CGACGCCGCGTGAGTGAGGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAGAATGACGGTACCTGA CTAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0079847 TGGGGAATATTGCACAATGGAGGGAACTCTGATGCAG 173 2 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTATGTAA AGCTCTGTCAGCAGGGAAGAAAGTGACGGTACCTGAA AAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0080400 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 174 5 CGACGCCGCGTGAGTGAAGAAATATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAG TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016481 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 175 4 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTATGTAA AGCTCTATCAGCAAGGAAGAAAAAAGACGGTACTTGA CTAAGAAGCCCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0050740 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 176 9 CGACGCCGCGTGGGTGAAGAAGTATTTCGGTATGTAA AGCCCTATCAGCAGGGAAGAAGATGACAGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000995 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 177 2 CGACGCCGCGTGGGTGAAGGAGTACTCCGGTATGTAA AGCCCTATCGGCAGGGAAGAAGATGACGGTACCTGAC TAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0083254 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 178 9 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAGTGACAGTACCTGAG TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0001347 TGGGGGATATTGGACAATGGGGGGAACCCTGATCCAG 179 6 CGACGCCGCGTGAGTGAAGAAGTATCTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAGAAATGACGGTACCT GAGTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000001 TGGGGGATATTGGACAATGGGGGGAACCCTGATCCAG 180 2 CGACGCCGCGTGAGTGAAGAAGTATCTCGGTATGTAA AGCTCTGTCAGCAGGGAAGAAAGAAATGACGGTACCT GACCAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080806 TGGGGGATATTGGACAATGGGGGGAACCCTGATCCAG 181 5 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTGTCAGCAGGGAAGAAAGAAATGACGGTACCT GAAGAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0081662 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 182 5 CGACGCCGCGTGGGTGAAGGAGTGCTTCGGCATGTAA AGCCCTATCGGCAGGGAAGAAGAAGGACGGTACCTG ACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016460 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 183 5 CGACGCCGCGTGGGTGAAGAAGCGCCCCGGCGCGTAA AGCCCTATCGGCAGGGAAGAAGATGACGGTACCTGGC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0023209 GGGGATATTGCACAATGGGGGAACCCGTGATGCAGCG 184 6 ACGCCGCGTGGGTGAAGAAGCGCCCCGGCGCGTAAA GCCCTATCGGCAGGGAAGAAGATGACGGTACCTGGCT AAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0003150 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 185 2 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGAACGAAGAAGACGGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0113068 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 186 3 CGACGCCGCGTGAGTGAAGAAGTAATTCGTTACGTAA AGCTCTATCAGCAGGAAAGAAAGAAGACGGTACCTG ACTAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0113935 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 187 5 CGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCGGGGAAGAGAATGACGGTACCCGAC TAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0085159 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 188 9 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAGATGACAGTACCTGAA TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0001004 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 189 7 CGACGCCGCGTGAGCGAGGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016413 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 190 5 CAACGCCGCGTGAGCGATGAAGGTCTTCGGATTGTAA AGCTCTGTCGCAGGGGACGAAGTATGACGGTACCCTG TAAGAAAGCCCCGGCAAACTACGTGCC SEQ_ID_NO_ R_U0003405 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 191 0 CGACGCCGCGTGAGCGAAGAAGTATCTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAGAATGACGGTACCTGA GTAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0113967 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 192 0 CGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAA CAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0003367 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 193 0 CAACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCACCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0003369 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 194 3 CGACGCCGCGTGAGTGAAGGAGTACTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAGCAAGACGGTACCTGA CCAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000258 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 195 3 CGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0004412 TGGGGAATATTGGGCAATGGAGGCAACTCTGACCCAG 196 9 CAACGCCGCGTGAGCGATGAAGGTCTTCGGATTGTAA AGCTCTTTAAGTGGGGACGAAGAAAGTGACTGTACCC ACAGAATAAGCCTCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0004265 TGGGGAATATTGGGCAATGGAGGAAACTCTGACCCAG 197 3 CAACGCCGCGTGAATGATGAAGGTCTTCGGATTGTAA AGTTCTTTTCTAAGGGAAGAAGAAAGTGACGGTACCT TAGGAATAAGCCTCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0085532 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 198 8 CAATGCCGCGTGGGTGAAGAAGTACCCCGGTATGTAA AGCCCTATCAGCAGGGAAGAAAATGACGGTACCTGGC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016419 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 199 6 CGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAAGGAAGATAATGACGGTACTTGAC TAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0016425 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAG 200 6 CAACGCCGCGTGAAGGAAGAAGGGTTTCGGCTCGTAA ACTTCTATCAACAGGGACGAAGGAAGTGACGGTACCT GAATAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000307 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 201 9 CAACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCTCCGGCTAAATACGTGCC SEQ_ID_NO_ R_U0000240 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 202 4 CGACGCCGCGTGGAGGAAGAAGGCCCTCGGGTTGTAA ACTCCTGTCTTTGGGGACGATAATGACGGTACCCAAG GAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080437 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 203 5 CGACGCCGCGTGGAGGAAGAAGGCCCTCGGGTTGTAA ACTCCTGTCTTCGGGGACGATAATGACGGTACCCGAG GAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0044387 TGGGGGATATTGCACAATGGGGGGAACCCTGATGCAG 204 2 CGACGCCGCGTGAGCGAAGAAGATCTTCGGATTGTAA AGCTCTGTCTTAGGGGACGATGATGACGGTACCCTGA GAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000012 TGGGGGATATTGCGCAATGGGGGCAACCCTGACGCAG 205 8 CAACGCCGCGTGAAGGATGAAGGTTTTCGGATTGTAA ACTTCTTTTCTTAAGGACGAAATTTGACGGTACTTAAG GAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000277 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 206 7 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTAAGAGGGACGAAGGAAGTGACGGTACCT CTTGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000116 TGAGGGATATTGGTCAATGGGGGAAACCCTGAACCAG 207 6 CAACGCCGCGTGAGGGAAGACGGTCTTCGGATTGTAA ACCTTTGTCCTCTGTGAAGATAATGACGGTAGCAGAG GAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000208 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 208 7 CAACGCCGCGTGAAGGAAGAAGGTCTTCGGATTGTAA ACTTTTGTCCTTGGTGAAGATAATGACGGTAGCCAAG GAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000809 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 209 8 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGTCAGGGAAGAGCAGAAGACGGTACCTG ACGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000098 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 210 1 CGACGCCGCGTGTGGGAAGACGGTCCTCTGGATTGTA AACCACTGTCCCCAGGGACGAAGATGACGGTACCTGG GGAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0043629 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 211 2 CGATGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAA ACTCCTGTCGACAGGAAAGAAAAAGGACTGTACCTGT CAAGAAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000255 TGGGGAATATTGCACAATGGGGGGAACCCTGATGCAG 212 1 CGATGCCGCGTGGAGGAAGAAGGTTTTCGGATTGTAA ACTCCTGTCTTAAAGGACGATAATGACGGTACTTTAG GAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016429 TGGGGAATATTGCACAATGGAGGAAACTCTGATGCAG 213 7 CGATGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTCTTAAGGGACGATAATGACGGTACCTTAG GAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080693 TGGGGGATATTGCACAATGGAGGGAACTCTGATGCAG 214 7 CGATGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTGGACAGAGACGATAATGACGGTATCTGTC AAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000272 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 215 3 CGATGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTGGAGGGGGACGATAATGACGGTACCCCTT AAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000487 TGGGGGATATTGGACAATGGGGGAAACCCTTATCCAG 216 8 CGACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTCAGCGGGGACGATAATGACGGTACCCGCG GAGGAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0114298 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 217 2 CGACGCCGCGTGAAGGAAGACGGTCTTCGGATTGTAA ACTTTAGTACTCAGGGACGAAGAAATGACGGTACCTG AGGTTAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080688 TGGGGGATATTGCGCAATGGGGGAAACCCTGACGCAG 218 4 CAACGCCGCGTGAAGGAAGAAGGTTTTCGGATTGTAA ACTTCTTTTATTAAGGACGAAAGATGACGGTACTTAAT GAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0081053 TGGGGAATATTGGGCAATGGACGCAAGTCTGACCCAG 219 1 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGTCAGGGAAGAGAAGAAGACGGTACCTG ACGAACAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000014 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 220 9 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGACAGGGAAGAGCAGAAGACGGTACCTG TCGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000450 TGGGGGATATTGCGCAATGGGGGCAACCCTGACGCAG 221 1 CAACGCCGCGTGAAGGATGAAGGTTTTCGGATTGTAA ACTTCTTTTATTAAGGACGAATTTTGACGGTACTTAAT GAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0013288 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 222 2 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTAAGAGGGAAGAGCAGAAGACGGTACCTC TTGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080038 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCAG 223 7 CAACGCCGCGTGAGGGAAGAAGGCTTTCGGGTTGTAA ACCTCTTTTACCAGGGACGAAGGACGTGACGGTACCT GGAGAAAAAGCAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000090 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCAG 224 8 CAACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAA ACTTCTTTTACCAGGGACGAAGGACGTGACGGTACCT GGAGAAAAAGCAACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0020438 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 225 6 CAACGCCGCGTGAAGGAAGAAGGCCTTCGGGTTGTAA ACTTCTTTTAAGAGGGACGAAGAAAGTGACGGTACCT CTTGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0079945 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 226 3 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGAGAGGGACGAAACAAATGACGGTACCT CTTGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080607 TGGGGAATATTGGGCAATGGGCGGAAGCCTGACCCAG 227 1 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTCTTGGGGACGAAGAAAGTGACGGTACCC AAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0113290 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 228 7 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGAGGGGGACGAAGGATGTGACGGTACCC CTTGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0046333 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 229 7 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTCTTGGGGACGAAGAAAGTGACGGTACCC GAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0081299 TGGGGAATATTGCACAATGGGGGAAACCCTGATGCAG 230 4 CGACGCCGCGTGGGTGAAGAAGTATTTCGGTATGTAA AGCCCTATCAGCAGGGAAGATCATGACGGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0001001 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 231 8 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTCTGAGGGACGAAGCAAGTGACGGTACCT TAGGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0016472 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 232 0 CAACGCCGCGTGAAGGAAGAAGGCTTTCGGGTTGTAA ACTTCTTTTGACAGGGAAGAGGAGAAGACGGTACCTG TCGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000441 TGGGGAATATTGGGCAATGGGCGCAAGCCTGACCCAG 233 8 CAACGCCGCGTGAAGGAAGAAGGCCCTCGGGTTGTAA ACTTCTTTTATCAGGGACGAAGAAGTGACGGTACCTG ATGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0020815 TGGGGAATATTGCGCAATGGGGGAAACCCTGACGCAG 234 3 CAACGCCGCGTGATTGAAGAAGGCCTTCGGGTTGTAA AGATCTTTAATCGGGGACGAATTTTGACGGTACCCGA AGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0003087 TGGGGAATATTGCGCAATGGGGGAAACCCTGACGCAG 235 0 CAACGCCGCGTGATTGAAGAAGGCCCTCGGGTTGTAA AGATCTTTAATCGGGGACGAAGAATGACGGTACCCGA AGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0083779 TGGGGAATATTGCGCAATGGGGGAAACCCTGACGCAG 236 7 CAACGCCGCGTGAGTGAAGAAGGCCTTCGGGTTGTAA AGCTCTTTAATCAGGGACGAAGAACGACGGTACCTGA AGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0044980 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 237 4 CAACGCCGCGTGAAGGAAGAAGGTCTTCGGATTGTAA ACTTCTTTTATCAGGGACGAAGGAAGTGACGGTACCT GATGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0043633 TCGGGAATATTGCGCAATGGAGGCAACTCTGACGCAG 238 2 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCCACAGGGAAGAAAAGGACTGTACCTGTG AAGAAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000343 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 239 5 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCCACAGGGAAGATAAAAGACTGTACCTGT GAAGAAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0019867 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 240 3 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGATAGGGAAGAAAAAAGACTGTACCTAT CAAGAAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000272 TCGGGAATATTGCGCAATGGAGGGAACTCTGACGCAG 241 0 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTTTAGTCAGGGAAGAAAGCAGACGGTACCTGA AGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0019570 TCGGGAATATTGCACAATGGAGGAAACTCTGATGCAG 242 7 TGACGCCGCGTGCAGGAAGAAGGTTTTCGGATTGTAA ACTGCTTTAGACAGGGAAGAAAAAAGACAGTACCTGT AGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000268 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 243 6 TGACGCCGCGTATAGGAAGAAGTTTTTCGGAATGTAA ACTATTGTCGTTAGGGAAGAGAAAGGACAGTACCTAA GGAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000895 TCGGGAATATTGCGCAATGGAGGGAACTCTGACGCAG 244 9 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGTTAGGGAAGAAAAAAGACAGTACCTAA GGAGGAAGCCCCGGCTAACTATGTGCC SEQ_ID_NO_ R_U0003435 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 245 1 TGACGCCGCGTATAGGAAGAAGGTCTTCGGATTGTAA ACTATTGTCGTTAGGGAAGAGAAAGGACAGTACCTAA GGAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0043700 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 246 9 TGACGCCGCGTGCAGGAAGAAGGTTTTCGGATTGTAA ACTGCTTTAGACAGGGAAGAAACAAATGACAGTACCT GTAGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0003248 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 247 6 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGTGAGGGAAGAAATTGACAGTACCTCAG GAGGAAGCTCCGGCTAACTATGTGCC SEQ_ID_NO_ R_U0000099 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 248 9 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGTTAGGGAAGAGAAAGGACAGTACCTAA GGAGGAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000220 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 249 1 TGACGCCGCGTGCAGGAAGAAGGTTTTCGGATTGTAA ACTGCTTTAGACAGGGAAGAAAGAAATGACGGTACCT GTAGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000189 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 250 1 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGTTAGGGAAGATAAAAGACTGTACCTAA GGAGGAAGCCCCGGCTAACTATGTGCC SEQ_ID_NO_ R_U0080366 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 251 5 TGACGCCGCGTATAGGAAGAAGTTTTTCGGAATGTAA ACTATTGTCATTAGGGAAGAGAAAGGACGGTACCTAA GGAGGAAGCCCCGGCTAACTATGTGCC SEQ_ID_NO_ R_U0002711 TCGGGAATATTGCGCAATGGAGGAAACTCTGACGCAG 252 1 TGACGCCGCGTATAGGAAGAAGGTTTTCGGATTGTAA ACTATTGTCGTTAGGGAAGAAAAAAGACAGTACCTAA GGAGGAAGCCCCGGCTAACTATGTGCC SEQ_ID_NO_ R_U0045415 TTGGGAATATTGGACAATGGAGGAAACTCTGATCCAG 253 7 TGACGCCGCGTGAAGGAAGAAGGTCTTCGGATTGTAA ACTTATTTTGTCAGGGAAGAATAAATGACTGTACCTG AAGAAAAAGCACCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0008017 TGGGGAATATTGCGCAATGGGGGAAACCCTGACGCAG 254 4 CAACGCCGCGTGCAGGAAGAAGGTCTTCGGATTGTAA ACTGTTGTCGCAGGGGAAGAAGACAGTGACGGTACCC TGTGAGAAAGTCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080330 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 255 2 CAACGCCGCGTGGAGGAAGAAGGTTTTCGGATCGTAA ACTCCTGTCCTAAGAGACGAGGAAGAGACGGTATCTT AGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0003220 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 256 8 CAACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTCCTAAGTGACGAAGGAAGTGACGGTAGCT TAGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000111 TGGGGAATATTGGGCAATGGGCGAAAGCCTTACCCAG 257 6 CAACGCCGCGTGAGGGAAGAAGGTTTTCGGATTGTAA ACCTCTGTCCTGGGGGACGAAGGAAGTGACGGTACCC CGGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080770 TGGGGAATATTGGGCAATGGGGGAAACCCTGACCCAG 258 4 CAACGCCGCGTGAAGGAAGAAGGTTTTCGGATCGTAA ACTTCTATCCTTGGTGAAAATGATGATGGTAGCCAAG AAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000027 TGGGGAATATTGGGCAATGGGCGAAAGCCTGACCCAG 259 2 CAACGCCGCGTGAGGGAAGAAGGGTTTCGGCTCGTAA ACCTCTGTCCTATGGGACGAAGGAAGTGACGGTACCA TAGGAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0080527 TGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAG 260 7 CAACGCCGCGTGAGCGAAGAAGGTCTTCGGATCGTAA AGCTCTGTCCTTGGGGAAGATAATGACGGTACCCAAG GAGGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0113623 TGGGGAATATTGGGCAATGGAGGCAACTCTGACCCAG 261 8 CAACGCCGCGTGAATGAAGAAGGTCCTAGGATTGTAA AGTTCTTTTATGATAGACGAATAAAATGACGGTATAT CATGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0084863 TGGGGAATATTGGGCAATGGAGGCAACTCTGACCCAG 262 9 CAACGCCGCGTGAATGAAGAAGGCCTTCGGGTTGTAA AGTTCTTTAATGGGGGACGAAGAAAGTGACGGTACCC CAAGAATAAGCCACGGCTAACTACGTGCC SEQ_ID_NO_ R_U0000424 TGGGGGATATTGCACAATGGGGGAAACCCTGATGCAG 263 9 CGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAA AGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGAC TAAGAAGCCCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0001209 TTAGGAATATTCGTCAATGGGGGAAACCCTGAACGAG 264 6 CAATGCCGCGTGAGTGATGACGGTCTTTATGATTGTA AAACTCTGTTGTAAGGAAAGAACCCTTATCATAGGAA ATGATGATAAGTTGACGGTACCTTACCAGAAAGCCCC GGCTAACTACGTGCC SEQ_ID_NO_ R_U0115212 TAGGGAATTTTCGGCAATGGGGGGAACCCTGACCGAG 265 2 CAACGCCGCGTGAACGAAGAAGTTATTCGTAATGTAA AGTTCTTTTATCAGGGAAGAAAAGAAGGGAATTGACG GTACCTGATGAATAAGCTCCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0112319 TGGGGAATCTTCCGCAATGGGCGAAAGCCTGACGGAG 266 9 CGACGCCGCGTGAGTGAAGAAGGTCTTCGGACCGTAA AGCTCTTTTGTTGCAGGCGAAAGGACTTAAGAGGAAA TGCTTAAGTTAAGACGGTATGGAACGAATAAGCCACG GCTAACTACGTGCC SEQ_ID_NO_ R_U0000073 TAGGGAATCTTTCACAATGGGCGAAAGCCTGATGGAG 267 7 CAACGCCGCGTGCAGGATGAAGGCCTTCGGGTTGTAA ACTGCTTTTATAAGCGAGAAATATGATGGTAACTTAT GAATAAGGATCGGCTAACTACGTGCC SEQ_ID_NO_ R_U0082204 TGGGGAATTTTGGACAATGGACGGAAGTCTGATCCAG 268 0 CAACGCAGCGTGAAGGACGAAGGTTCTCGGATTGTAA ACTTCTTTTGCAGGGGAAGAAAAAAATGACGGTACCC TGTGAATAAGCCACGGCTAACTACGTGCC

In the above detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be used, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, may be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

The present disclosure is not to be limited in terms of the particular embodiments described in this application, which are intended as illustrations of various aspects. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this disclosure is not limited to particular methods, reagents, compounds, compositions or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.

It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.”

In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” and the like include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.

From the foregoing, it will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration, and that various modifications may be made without departing from the scope and spirit of the present disclosure. Accordingly, the various embodiments disclosed herein are not intended to be limiting, with the true scope and spirit being indicated by the following claims. 

What is claimed is:
 1. A method for increasing a first gut microbiota population while simultaneously decreasing a second gut microbiota population in a subject having obesity, diabetes or insulin insensitivity to increase short-chain fatty acid level in the subject or reducing subject insulin sensitivity, comprising administering to the subject berberine at a dosage of from about 50 mg/Kg body weight to about 400 mg/Kg body weight, wherein the first gut microbiota population comprises, Allobaculum, Bacteroides, Blautia, Butyricicoccus, Dorea, Holdemania, Lawsonia, Parabacteroides, Phascolarctobacterium, Sedimentibacter, or a combination thereof; wherein the second gut microbiota population comprises Anaeroplasma, Bifidobacterium, Butyrivibrio, Coprococcus, Fastidiosipila, Marvinbryantia, Oribacterium, Roseburia, Ruminococcus, TM7_genera_incertae_sedis, or a combination thereof.
 2. The method of claim 1, wherein the first gut microbiota population comprises a bacterium whose V3 region of 16S rRNA gene sequence has at least about 95% similarity with a nucleic acid sequence selected from a group consisting of SEQ ID NO: 1-93.
 3. The method of claim 1, wherein the second gut microbiota population comprises a bacterium whose V3 region of 16S rRNA gene sequence has at least about 95% similarity with a nucleic acid sequence selected from a group consisting of SEQ ID NO: 94-268. 